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Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment

Leukemia volume 24, pages 903–907 (2010)Cite this article

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In contrast to favorable cure rates in childhood acute lymphoblastic leukemia, prognosis in infant leukemia occurring within the first year of life remained poor, despite intense effort in therapy optimization in this critical subgroup. The early clinical manifestation, detection of leukemic clone-specific gene rearrangements in neonatal blood spots and high concordance rates in monochorial twins argue for a prenatal origin in most, if not all cases of infant leukemia.1 A hallmark of infant leukemia is the high prevalence of chromosomal rearrangements involving the MLL gene at chromosome band 11q23, detectable in about two-thirds of cases. The most frequent partner genes are AF4 (MLLT2), AF9 (MLLT4) and ENL (MLLT3), accounting for ∼85% of all MLL-positive cases.2 With respect to clinical course and biological features, infant leukemia exhibits different characteristics to a phenotypically and cytogenetically similar disease in older age.3, 4

A high rate of breakpoints located in the telomeric portion of the MLL breakpoint cluster region (BCR), similar to therapy-induced acute leukemia associated with topoisomerase II inhibitors, suggested a similar mechanism for MLL rearrangement generation in infant leukemia. Other DNA features, such as scaffold-attachment regions (SAR), DNAse I hypersensitivity sites and initiation sites of apoptotic nucleases, have been discussed to be involved in alternative break mechanisms.1 The aim of this study was to assess breakpoint distribution within the MLL gene in a cohort of 59 infants, in comparison with pediatric and adult patients, to evaluate age-dependent breakpoint distribution and association of recombination-related sequence motifs.

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Acknowledgements

We thank all members of the participating INTERFANT-99 study groups for providing patients samples and clinical data. This study was supported by a Wilhelm–Sander Foundation grant to MM and TL. RJ was supported by a grant from the Carreras Foundation. ERP-G was supported by GENAU-CHILD Project GZ200.136/1—VI/1/2005 and the St Anna Kinderkrebsforschung.

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Authors and Affiliations

  1. Department of Pediatrics, University of Erlangen-Nuremberg, Erlangen, Germany

    R Jung, U Jacobs, M Krumbholz, T Langer, W Rascher & M Metzler

  2. ACOMED Statistik, Statistical Analyses, Leipzig, Germany

    T Keller

  3. Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Bicocca, Italy

    P De Lorenzo & M G Valsecchi

  4. Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands

    V H J van der Velden & J J M van Dongen

  5. Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    A Moericke, M Stanulla & M Schrappe

  6. Department of Pediatric Hematology and Oncology, University of Giessen, Giessen, Germany

    A Teigler-Schlegel

  7. Children's Cancer Research Institute (CCRI) at St Anna Children's Hospital, Vienna, Austria

    E R Panzer-Gruemayer

  8. Department of Oncology/Hematology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands

    M L den Boer & R Pieters

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  1. R Jung
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Correspondence to M Metzler.

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Jung, R., Jacobs, U., Krumbholz, M. et al. Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment. Leukemia 24, 903–907 (2010). https://doi.org/10.1038/leu.2010.14

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